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We thank Dr Mendall for the interest regarding our study “Obesity is associated with increased risk of Crohn’s disease, but not ulcerative colitis: A pooled analysis of 5 prospective cohort studies,”1Chan S.S.M. et al.Clin Gastroenterol Hepatol. 2022; 20: 1048-1058Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar and drawing our attention to studies reporting an association between low body mass index (BMI) and risk of Crohn’s disease (CD). In the work by Mendall and colleagues, men in early adulthood (age 18–21 years) and women (age 27–34 years) with a low baseline BMI (<18.5 kg/m2) were associated with an increased risk of developing CD in later life.2Mendall M.A. et al.Sci Rep. 2019; 19: 6360Crossref Scopus (8) Google Scholar,3Mendall M. et al.PLoS One. 2018; 13e0190600Crossref PubMed Scopus (19) Google Scholar Our study focused on obesity as defined by a BMI ≥30 kg/m2 and adjusted for numerous covariates (ie, total physical activity, total energy intake, dietary fiber and fat intake, smoking, sex, age at baseline). As stated in our methodology we specifically excluded those patients considered to be underweight (BMI <18.5 kg/m2) at recruitment and those who developed inflammatory bowel disease within 2 years of recruitment. This was done to reduce the risk of reverse causality because a low BMI may represent undiagnosed inflammatory bowel disease, another undiagnosed disease, or be a general indicator of poor health. Mendall and colleagues did consider the possibility of such biases in their studies but believed that the association between low BMI and risk for developing CD in men and women was unlikely to be explained by preclinical disease because the median time between baseline BMI measurement and CD diagnosis was ∼28 years and ∼7 years, respectively. As highlighted by the authors other limitations of their studies included the inability to control for diet and the absence of BMI data in later life. In our study, joint multivariable analyses of early adulthood BMI found that those with the greatest weight gain from early adulthood to midlife were at higher risk of developing CD regardless of their early adulthood BMI. Therefore, it may be that weight gained between early adulthood and midlife contributed to the associations observed by Mendall and colleagues rather than low BMI per se. Regardless of the potential biases and difficulties in interpreting associations between low BMI and CD, we would have been unable to fully assess for associations between low BMI and risk of developing CD because of the limited numbers of cases among this group in our cohorts. Obesity and Risk of Crohn’s Disease Half the StoryClinical Gastroenterology and HepatologyPreviewI read with great interest the recent study by Chan and colleagues entitled “Obesity is Associated With Increased of Crohn’s disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Studies.”1 Full-Text PDF